FOCAL OR INSULAR NECROSIS PRODUCED BY THE BACILLUS OF TUBERCULOSIS.
1. It must be accepted from a comparison between the histological changes described in the focal necroses due to abrin and ricin, diphtheria, eclampsia, blood-serum intoxication, typhoid fever, lobar pneumonia and glanders, and those described here in three cases of tuberculosis, that the last are also instances of focal necrosis. 2. It may be claimed that the areas of necrosis in the three cases of tuberculosis had their origin in ischaemia, for the reason that they were numerous in the spleen and were not found in the kidney. Against such an explanation of their causation are the facts: that other forms of necrosis affect frequently the spleen and seldom the kidney; that thrombosis of vessels or any fixed relation of the areas in the spleen to blood-vessels could not be established; that the tubercle bacilli were invariably present; and lastly and of no slight importance, that these necroses were all present in cases of marked marasmus. 3. That the areas of necrosis in these three cases might be phenomena resulting from a mixed infection with pyogenic bacteria is possible, but no groups, colonies or even single bodies could be found which answered to the requirements in shape or staining properties for such bacteria. Even were it the case that the focal necroses here presented are the histological lesions of a septicaemia occurring as a complication of tuberculosis, the presence of the bacillus of tuberculosis in the areas of necrosis would still require explanation. 4. Lastly, it is not unreasonable to suppose that a diminished resistance on the part of the tissues incidental to marasmus is an important factor in the production of these necrotic lesions.


Energetics of defects on graphene through fluorination.
Functionalized graphene sheets (FGSs) comprise a unique member of the carbon family, demonstrating excellent electrical conductivity and mechanical strength. However, the detailed chemical composition of this material is still unclear. Herein, we take advantage of the fluorination process to semiquantitatively probe the defects and functional groups on graphene surface. Functionalized graphene sheets are used as substrate for low-temperature (<150 °C) direct fluorination. The fluorine content has been modified to investigate the formation mechanism of different functional groups such as C-F, CF2, O-CF2 and (C=O)F during fluorination. The detailed structure and chemical bonds are simulated by density functional theory (DFT) and quantified experimentally by nuclear magnetic resonance (NMR). The electrochemical properties of fluorinated graphene are also discussed extending the use of graphene from fundamental research to practical applications.


Antioxidant activity and sex differences of acute vascular effects of amiodarone in advanced atherosclerosis.
Sexual dimorphisms of atherosclerosis and the susceptibility to arrhythmias and antiarrhythmic treatment have been reported. This study investigated acute effects of amiodarone on endothelium-dependent relaxation in the aorta of male and female apoE0 mice with advanced atherosclerosis. Amiodarone tissue uptake was quantified by high-performance liquid chromatography, and xanthine oxidase-dependent superoxide anion formation was investigated in vitro in presence or absence of amiodarone. Incubation with amiodarone for 30 min improved endothelium-dependent relaxation, which was associated with rapid vascular accumulation of amiodarone (P < 0.001) that was sex-dependent. In males, reduced endothelium-dependent relaxation was improved by amiodarone (from 88 +/- 3% to 100 +/- 2%, P < 0.01). Spontaneous phasic contractions, which were greater in females than in males (P < 0.001), were completely abolished by amiodarone (P < 0.0001). Amiodarone also inhibited generation of superoxide anion (P < 0.0001). These data show that amiodarone rapidly accumulates in atherosclerotic vascular tissue, abolishes vascular autorhythmicity, and improves endothelium-dependent function in atherosclerotic arteries. Antioxidant and vasodilator effects following amiodarone administration may contribute to its antiarrhythmic effects.


Alternative diets for Chrysomya putoria, an Old World screwworm fly.
Abstract The purpose of this study was to evaluate the post-embryonic development of Chrysomya putoria (Wiedemann 1818) (Diptera: Calliphoridae) reared on a diet of gizzard or gizzard/agar homogenate, with a diet of beef used as the control. Four replicates per treatment were performed (60 mL of each diet). The gizzard (60%), distilled water, and agar homogenate were combined in a blender. Each replicate consisted of 40 newly hatched larvae of C. putoria (5(th) generation). Each glass beaker containing a diet was inserted into a larger flask containing sawdust, which was covered with a nylon cloth held in place by an elastic band. The larvae were weighed and stored in test tubes sealed with a nylon cloth and an elastic band. The average temperature, measured with a thermohygrograph, was 20.6 °C, and the average relative humidity was 67.7%. The variation in the mean weight of mature larvae and in the duration of the larval, pupal, and total stages (newly hatched larvae to imagoes) were analyzed by Student's t-test (α = 5%), while viability was compared by ANOVA. The sex ratio was evaluated by the chi-squared test. The average duration of the period from the larval to imago stage was 8.868 days on the beef diet, 8.676 on the gizzard diet, and 9.067 on the gizzard/agar homogenate diet. Larval survival rates on these diets were 98, 92, and 73%, respectively, while pupal viabilities were 98, 91, and 71%, respectively, and larva-to-imago viabilities were 93, 83, and 64%, respectively. The duration of the pupal period differed significantly between the blowflies reared on the beef and gizzard/agar homogenate diets. The two diets proved to be good alternatives for rearing C. putoria.


Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse.
Endoplasmic reticulum (ER) stress has been implicated in a wide variety of neurodegenerative disorders of the central nervous system (CNS). This study was designed to elucidate the role of ER stress in photoreceptor apoptosis in the rd1 mouse. Photoreceptor apoptosis in the rd1 mouse was detected by terminal dUTP transferase nick-end labeling (TUNEL). Protein expressions of ER stress sensors, including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2alpha (eIF2alpha), and phospho-pancreatic ER kinase (PERK), were examined by immunofluorescence and Western blot assays. Accompanying photoreceptor apoptosis in the rd1 mouse, the protein expressions of GRP78/BiP, caspase-12, phospho-eIF2alpha, and phospho-PERK were upregulated in a time-dependent manner. The upregulation of these proteins coincided with or preceded photoreceptor apoptosis. At the peak of their expression, these proteins were primarily located in the photoreceptor inner segments, the outer nuclear layer, or both. ER stress plays an important role in photoreceptor apoptosis in the rd1 mouse. Therefore, ER stress modulators may be strong candidates as therapeutic agents in the treatment of retinal degenerative diseases.


Endometriosis persisting after castration: clinical characteristics and results of surgical management.
To identify the clinical characteristics and response to surgical treatment of endometriosis-associated pain in castrated women. In a prospective, longitudinal observational study, 75 patients with previous castration had biopsy-proven endometriosis excised surgically. Anatomical characteristics of disease were studied using pelvic mapping and compared to the findings in non-castrated women with endometriosis. Preoperative and postoperative verbal analogue pain scales were used to gauge the response to excision of endometriosis. Patients treated surgically for endometriosis following castration were significantly older (37.8 +/- 8.1 versus 31.3 +/- 6.9 years, mean +/- standard deviation; 95% confidence interval [CI] 4.9-8.1) and slightly more likely to have intestinal involvement (risk ratio 1.3, 95% CI 0.94-1.8) than non-castrated endometriosis patients. Most had marked alleviation of pain after excision of endometriosis. Endometriosis can remain symptomatic after castration, with or without estrogen therapy. In such patients, there is a 33% frequency of intestinal involvement. At castration, consideration should be given to removal of invasive peritoneal and intestinal disease. Symptom improvement occurs in most patients after excision of endometriosis.


Genome-wide scan demonstrates significant linkage for male sexual orientation.
Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28. We conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date. We identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research. Results, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.


Mercury-induced Oxidative Stress May Adversely Affect Pregnancy Outcome among Dental Staff: A Cohort Study.
Dental staff may be at increased risk of adverse pregnancy outcome secondary to their chronic exposure to mercury. To investigate obstetric outcome among dental staff and explore the oxidative stress induced by mercury exposure. A cohort of 64 pregnant dental staff (exposed group) and 60 pregnant employees (non-exposed group) were studied. Urinary mercury level and blood antioxidant activity were measured. Participants were followed to assess their obstetric outcome. The exposed group had a higher mean urinary mercury level and a lower blood antioxidant activity during the three trimesters compared to non-exposed group (p<0.001). Women in the exposed group were experienced more frequently spontaneous abortion and pre-eclampsia (p<0.05). Babies born to the women in the exposed group tended to be smaller for gestational age compared to those of non-exposed group (p<0.001). Pregnant dental staff suffered higher odds of developing spontaneous abortion and pre-eclampsia and giving birth to babies smaller for gestational age. This may be linked to oxidative stress induced by exposure to mercury.


Dietary pattern derived by reduced rank regression and depressive symptoms in a multi-ethnic population: the HELIUS study.
To investigate the association of dietary patterns derived by reduced rank regression (RRR) with depressive symptoms in a multi-ethnic population. Cross-sectional data from the HELIUS study were used. In total, 4967 men and women (18-70 years) of Dutch, South-Asian Surinamese, African Surinamese, Turkish and Moroccan origin living in the Netherlands were included. Diet was measured using ethnic-specific food frequency questionnaires. Depressive symptoms were measured with the nine-item patient health questionnaire. By performing RRR in the whole population and per ethnic group, comparable dietary patterns were identified and therefore the dietary pattern for the whole population was used for subsequent analyses. We identified a dietary pattern that was strongly related to eicosapentaenoic acid+docosahexaenoic acid, folate, magnesium and zinc (response variables) and which was characterized by milk products, cheese, whole grains, vegetables, legumes, nuts, potatoes and red meat. After adjustment for confounders, a statistically significant inverse association was observed in the whole population (B: -0.03, 95% CI: -0.06, -0.00, P=0.046) and among Moroccan (B: -0.09, 95% CI: -0.13, -0.04, P=0.027) and South-Asian Surinamese participants (B: -0.05, 95% CI: -0.09, -0.01, P=<0.001), whereas no statistically significant association was found in the remaining ethnic groups. No statistically significant associations were found between the dietary pattern and significant depressed mood in any of the ethnic groups. No consistent evidence was found that consumption of a dietary pattern, high in nutrients that are hypothesized to protect against depression, was associated with lower depressive symptoms across different ethnic groups.


Biochemical and immunological evaluation of donor-specific soluble HLA in the circulation of liver transplant recipients.
MHC antigens, normally expressed as integral membrane proteins, are also present in soluble form in the peripheral circulation. These soluble human leukocyte antigens (sHLA) are found at elevated levels in patients with a variety of infections as well as in organ transplant recipients. In liver transplant recipients, however, most of the circulating sHLA are of donor phenotype, especially during the early posttransplant period. Here we report the purification and characterization of sHLA of both recipient and donor origin from liver transplant recipients. It was observed that sHLA consisted of four major polypeptides having molecular mass of 44, 41, 35-37, and 12 kD complexed with IgM and IgG antibodies. Further analysis revealed that these immunoglobulins contained anti-HLA antibodies. Analysis of the affinity-purified materials by a number of approaches failed to detect any other fragment(s) of HLA class I heavy chain polypeptides smaller than 12 kD. No significant difference was observed in the biochemical nature of the sHLA of donor and recipient origin and they were similar to those found in normal individuals. Affinity-purified HLA-A3 inhibited the cytolytic activity of an HLA-A3-specific CD8+ T cell line, whereas, purified sHLA-A2 failed to inhibit anti-HLA-A3 CTL activity. Further, the proliferation of the T cell line was not inhibited by sHLA-A3. Thus, the inhibitory activity shown by sHLA was antigen-specific and directed against a functional subset of T lymphocytes. These results support the notion that sHLA may play an important regulatory role in the immune response to allograft in humans.


Meta-analysis of amyloid-cognition relations in cognitively normal older adults.
We conducted a meta-analysis of relationships between amyloid burden and cognition in cognitively normal, older adult humans. Methods of assessing amyloid burden included were CSF or plasma assays, histopathology, and PET ligands. Cognitive domains examined were episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Sixty-four studies representing 7,140 subjects met selection criteria, with 3,495 subjects from 34 studies representing independent cohorts. Weighted effect sizes were obtained for each study. Primary analyses were conducted limiting to independent cohort studies using only the most common assessment method (Pittsburgh compound B). Exploratory analyses included all assessment methods. Episodic memory (r = 0.12) had a significant relationship to amyloid burden. Executive function and global cognition did not have significant relationships to amyloid in the primary analysis of Pittsburgh compound B (r = 0.05 and r = 0.08, respectively), but did when including all assessment methods (r = 0.08 and r = 0.09, respectively). The domains of working memory, processing speed, visuospatial function, and semantic memory did not have significant relationships to amyloid. Differences in the method of amyloid assessment, study design (longitudinal vs cross-sectional), or inclusion of control variables (age, etc.) had little influence. Based on this meta-analytic survey of the literature, increased amyloid burden has small but nontrivial associations with specific domains of cognitive performance in individuals who are currently cognitively normal. These associations may be useful for identifying preclinical Alzheimer disease or developing clinical outcome measures.


A failure modes and effects analysis quality management framework for image-guided small animal irradiators: A change in paradigm for radiation biology.
Image-guided small animal irradiators (IGSAI) are increasingly being adopted in radiation biology research. These animal irradiators, designed to deliver radiation with submillimeter accuracy, exhibit complexity similar to that of clinical radiation delivery systems, including image guidance, robotic stage motion, and treatment planning systems. However, physics expertise and resources are scarcer in radiation biology, which makes implementation of conventional prescriptive QA infeasible. In this study, we apply the failure modes and effect analysis (FMEA) popularized by the AAPM task group 100 (TG-100) report to IGSAI and radiation biological research. Radiation biological research requires a change in paradigm where small errors to large populations of animals are more severe than grievous errors that only affect individuals. To this end, we created a new adverse effects severity table adapted to radiation biology research based on the original AAPM TG-100 severity table. We also produced a process tree which outlines the main components of radiation biology studies performed on an IGSAI, adapted from the original clinical IMRT process tree from TG-100. Using this process tree, we created and distributed a preliminary survey to eight expert IGSAI operators in four institutions. Operators rated proposed failure modes for occurrence, severity, and lack of detectability, and were invited to share their own experienced failure modes. Risk probability numbers (RPN) were calculated and used to identify the failure modes which most urgently require intervention. Surveyed operators indicated a number of high (RPN >125) failure modes specific to small animal irradiators. Errors due to equipment breakdown, such as loss of anesthesia or thermal control, received relatively low RPN (12-48) while errors related to the delivery of radiation dose received relatively high RPN (72-360). Errors identified could either be improved by manufacturer intervention (e.g., electronic interlocks for filter/collimator) or physics oversight (errors related to tube calibration or treatment planning system commissioning). Operators identified a number of failure modes including collision between the collimator and the stage, misalignment between imaging and treatment isocenter, inaccurate robotic stage homing/translation, and incorrect SSD applied to hand calculations. These were all relatively highly rated (90-192), indicating a possible bias in operators towards reporting high RPN failure modes. The first FMEA specific to radiation biology research was applied to image-guided small animal irradiators following the TG-100 methodology. A new adverse effects severity table and a process tree recognizing the need for a new paradigm were produced, which will be of great use to future investigators wishing to pursue FMEA in radiation biology research. Future work will focus on expanding scope of user surveys to users of all commercial IGSAI and collaborating with manufacturers to increase the breadth of surveyed expert operators.


Loss in long-storage-time optical cavities.
Long-storage-time Fabry-Perot cavities are a core component of many precision measurement experiments. Optical loss in such cavities is a critical parameter in determining their performance; however, it is very difficult to determine a priori from independent characterisation of the individual cavity mirrors. Here, we summarise three techniques for directly measuring this loss in situ and apply them to a high-finesse, near-concentric, 2 m system. Through small modifications of the cavity's length, we explore optical loss as a function of beam spot size over the 1-3 mm range. In this regime we find that optical loss is relatively constant at around 5 ppm per mirror and shows greater dependence on the positions of the beam spots on the cavity optics than on their size. These results have immediate consequences for the application of squeezed light to advanced gravitational-wave interferometers.


Acquisition of phase-shift fiber grating spectra with 23.5 femtometer spectral resolution using DFB-LD.
A novel method based on distributed-feedback laser diode (DFB-LD) continuous wavelength-scanning for acquiring precise spectra of phase-shift fiber gratings is presented. Compared to the traditional method, the spectral resolution retrieved by this method is only limited by the optical line-width of the light source, which can reach up to the order of femtometer and is much higher than that of high-resolution optical spectrum analyzer (generally on the order of picometer). In addition, a Signal-to-Noise Ratio (SNR) advantage can be provided owing to a much higher spectral density of DFB-LD than amplified spontaneous emission (ASE) source. Precise spectra of three phase-shift fiber grating samples have been obtained at a resolution of 23.5 femtometer.


Surface plasmons and magneto-optic activity in hexagonal Ni anti-dot arrays.
The influence of surface plasmons on the magneto-optic activity in a two-dimensional hexagonal array is addressed. The experiments were performed using hexagonal array of circular holes in a ferromagnetic Ni film. Well pronounced troughs are observed in the optical reflectivity, resulting from the presence of surface plasmons. The surface plasmons are found to strongly enhance the magneto-optic response (Kerr rotation), as compared to a continuous film of the same composition. The influence of the hexagonal symmetry of the pattern on the coupling between the plasmonic excitations is demonstrated, using optical diffraction measurements and theoretical calculations of the magneto-optic and of the angular dependence of the optical activity.


Different amino acid substitutions at the same position in the nucleotide-binding site of aspartate transcarbamoylase have diverse effects on the allosteric properties of the enzyme.
Site-directed mutagenesis was used to determine how the allosteric properties of aspartate transcarbamoylase (ATCase) are affected by amino acid replacements in the nucleotide binding region of the regulatory polypeptide chains. Amino acid substitutions were made for both Lys-60 and Lys-94 in the regulatory chain since those residues have been implicated by x-ray diffraction studies, chemical modification experiments, and site-directed mutagenesis as playing a role in binding CTP and ATP. Lys-60 was replaced by His, Arg, Gln, and Ala, and Lys-94 was changed to His. These mutant forms of ATCase exhibit bewildering changes in the allosteric properties compared to the wild-type enzyme as well as altered affinities for the nucleotide effectors. The enzyme containing His-60 lacks both homotropic and heterotropic effects and exhibits no detectable binding of nucleotides. In contrast, the holoenzymes containing either Gln-60 or Arg-60 retain both homotropic and heterotropic effects. Replacement of Lys-60 by Ala yields a derivative exhibiting altered heterotropic effects involving insensitivity to CTP and activation by ATP. The mutant enzyme containing His-94 in place of Lys exhibits cooperativity with reduced affinity for nucleotides. The multiple substitutions at Lys-60 in the nucleotide binding region of the regulatory chains of ATCase demonstrate that different amino acids in the same location can alter indirectly the delicate balance of interactions responsible for the allosteric properties of ATCase. The studies show that it is hazardous and frequently unwarranted from single amino acid replacements of a specific residue to attribute to that residue the properties observed for the wild-type enzyme.


Faster, cheaper, defined and efficient vitrification for immature porcine oocytes through modification of exposure time, macromolecule source and temperature.
Vitrification reduces the developmental competence of porcine immature oocytes. We investigated the effects of modifying various factors on the viability and development of oocytes after vitrification. These factors included: 1) exposure to the vitrification solution, 2) macromolecule addition (bovine serum albumin (BSA) or polyvinyl pyrrolidone (PVP)), 3) treatment with cytochalasin B, 4) equilibration temperature, and 5) vitrification method (microdrop or Cryotop). Oocytes were equilibrated and vitrified using medium containing ethylene glycol and propylene glycol. After warming, oocytes were subjected to in vitro maturation, stimulated parthenogenetically, and cultured in vitro. Survival rate, nuclear maturation, cleavage, development to the blastocyst stage and their quality were compared between the vitrified groups and the non-vitrified control group. It was found that 1) exposure to the vitrification solution for longer than 30 s was detrimental to embryo development; 2) replacement of BSA with PVP improved embryo development; 3) cytochalasin B treatment reduced the survival rates, but did not affect the blastocyst development rates, 4) equilibration at room temperature (25 °C) was the most beneficial, and 5) the microdrop method improved survival rates. With these adjustments, we were able to establish a simplified and defined cryopreservation system for porcine immature oocytes with improved efficacy.


[Neuro-ophthalmological complications of sinusitis].
Sinusitis is a frequent and very often under-diagnosed condition. Despite the constantly increasing number of antibiotics with improved efficacy, prevention of its complications remains difficult. The prevalence of these complications is estimated at 3.7%. Their clinical presentation is highly variable making the diagnosis difficult and thereby increasing mortality. In this article, historical, epidemiological, pathophysiological, clinical and therapeutic aspects of neuro-ophthalmological complications of sinusitis are reviewed. For didactic reasons, the various complications have been divided into extra-axial, intra-axial, vascular, and orbital. Specific paragraph have been devoted to sinusitis-related bone complications and pain syndromes. It's however obvious that various more or less complex associations of these complications can be seen in daily practice.


The dynamics of nitrous oxide emission from the use of mineral fertilizers in Russia.
The intensity of nitrous oxide (N2O) emission was considered based on literature data on the single input of mineral N (nitrogen) fertilizers into different agricultural soil types in Russia. Ambient environmental factors exert a combined effect on the process of gaseous nitrogen formation from fertilizers applied. To reduce the uncertainty of estimates as much as possible, only experimental results obtained under conditions similar to natural were selected for the assessments. Mineral nitric fertilizers were applied to soil at a rate of 40 to 75 kg/ha and the N2O emissions were measured for approximately 140 days. Daily average emission values varied from 0.08 to 0.45% of fertilizer nitrogen. Correspondingly, 1.26 and 2.38% of fertilizer nitrogen were emitted as N2O from chernozems and soddy podzols. In 1990, the use of fertilizers in Russian agricultural practices for 53 Gg N2O-N, which equates to approximately 6.1% of global nitrous oxide emissions from nitric fertilizers. Later, the emission dropped because of a decrease in the input of nitric fertilizers to agricultural crops, and in 1998, it constituted just 20.5% of the 1990 level. In the period from 2008 to 2012, the nitrous oxide emission is expected to vary from 0.5 to 65.0 Gg N2O-N due to possible changes in national agricultural development. In the most likely scenario, the use of mineral fertilizers in Russia will account for approximately 34 to 40 Gg N2O-N emissions annually from 2008-2012.


A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys.
One of the major challenges that must be met in developing an HIV-1 vaccine is devising a strategy to generate cellular immunity with sufficient breadth to deal with the extraordinary genetic diversity of the virus. Amino acids in the envelopes of viruses from the same clade can differ by >15%, and those from different clades can differ by >30%. It has been proposed that creating immunogens using centralized HIV-1 gene sequences might provide a practical solution to this problem. Such centralized genes can be generated by employing a number of different strategies: consensus, ancestral, or center of tree sequences. These computer-generated sequences are a shorter genetic distance from any two contemporary virus sequences than those contemporary sequences are from each other. The present study was initiated to evaluate the breadth of cellular immunity generated through immunization of rhesus monkeys with vaccine constructs expressing either an HIV-1 global consensus envelope sequence (CON-S) or a single patient isolate clade B envelope sequence (clade B). We show that vaccine immunogens expressing the single centralized gene CON-S generated cellular immune responses with significantly increased breadth compared with immunogens expressing a wild-type virus gene. In fact, CON-S immunogens elicited cellular immune responses to 3- to 4-fold more discrete epitopes of the envelope proteins from clades A, C, and G than did clade B immunogens. These findings suggest that immunization with centralized genes is a promising vaccine strategy for developing a global vaccine for HIV-1 as well as vaccines for other genetically diverse viruses.


Genetic similarity of circulating and small intestinal virus at the end stage of acute pathogenic simian-human immunodeficiency virus infection.
To understand the pathogenicity of acquired immune deficiency syndrome (AIDS), it is important to clarify where, when and how the virus replicates in the body of infected individuals. To identify the major virus replication site at the end stage of SHIV infection, we investigated the systemic tissues of SHIV-infected monkeys that developed AIDS-like disease. We quantified proviral DNA, and compared the mutation patterns of the viruses in various systemic tissues and in peripheral blood through phylogenetic analysis of the full genome sequence. We found that the amounts of proviral DNA detected in internal tissues were higher than those in peripheral blood mononuclear cells. In the sequence and phylogenetic tree analyses, the mutation patterns of the viruses in each tissue were generally different. However, the mutation pattern of the viruses in the jejunum and mesenteric lymph node were most similar to that of plasma viral RNA among the tissues examined in all three monkeys. In two of the three monkeys, which were euthanized earlier, viruses in the jejunum and mesenteric lymph node occupied the root position of the phylogenetic tree. Furthermore, in these tissues, more than 50% of SHIV-expressing cells were identified as macrophages based on co-expression of CD68. These results suggest that macrophages of the small intestine and/or mesenteric lymph node are the major virus production site at the end stage of SHIV infection of macaques.


Bayesian design strategies for synthetic biology.
We discuss how statistical inference techniques can be applied in the context of designing novel biological systems. Bayesian techniques have found widespread application and acceptance in the systems biology community, where they are used for both parameter estimation and model selection. Here we show that the same approaches can also be used in order to engineer synthetic biological systems by inferring the structure and parameters that are most likely to give rise to the dynamics that we require a system to exhibit. Problems that are shared between applications in systems and synthetic biology include the vast potential spaces that need to be searched for suitable models and model parameters; the complex forms of likelihood functions; and the interplay between noise at the molecular level and nonlinearity in the dynamics owing to often complex feedback structures. In order to meet these challenges, we have to develop suitable inferential tools and here, in particular, we illustrate the use of approximate Bayesian computation and unscented Kalman filtering-based approaches. These partly complementary methods allow us to tackle a number of recurring problems in the design of biological systems. After a brief exposition of these two methodologies, we focus on their application to oscillatory systems.


Hierarchical singleton-type recurrent neural fuzzy networks for noisy speech recognition.
This paper proposes noisy speech recognition using hierarchical singleton-type recurrent neural fuzzy networks (HSRNFNs). The proposed HSRNFN is a hierarchical connection of two singleton-type recurrent neural fuzzy networks (SRNFNs), where one is used for noise filtering and the other for recognition. The SRNFN is constructed by recurrent fuzzy if-then rules with fuzzy singletons in the consequences, and their recurrent properties make them suitable for processing speech patterns with temporal characteristics. In n words recognition, n SRNFNs are created for modeling n words, where each SRNFN receives the current frame feature and predicts the next one of its modeling word. The prediction error of each SRNFN is used as recognition criterion. In filtering, one SRNFN is created, and each SRNFN recognizer is connected to the same SRNFN filter, which filters noisy speech patterns in the feature domain before feeding them to the SRNFN recognizer. Experiments with Mandarin word recognition under different types of noise are performed. Other recognizers, including multilayer perceptron (MLP), time-delay neural networks (TDNNs), and hidden Markov models (HMMs), are also tested and compared. These experiments and comparisons demonstrate good results with HSRNFN for noisy speech recognition tasks.


Skin Color and Social Mobility: Evidence From Mexico.
In many Latin American countries, census data on race and skin color are scarce or nonexistent. In this study, we contribute to understanding how skin color affects intergenerational social mobility in Mexico. Using a novel data set, we provide evidence of profound social stratification by skin color, even after controlling for specific individual characteristics that previous work has not been able to include, such as individual cognitive and noncognitive abilities, parental education and wealth, and measures of stress and parenting style in the home of origin. Results indicate that people in the lightest skin color category have an average of 1.4 additional years of schooling and 53 % more in hourly earnings than their darkest-skinned counterparts. Social mobility is also related to skin color. Individuals in the darkest category are 20 percentile ranks lower in the current wealth distribution than those in the lightest category, conditional on parental wealth. In addition, results of a quantile regression indicate that the darkest group shows higher downward mobility.


Monoamine oxidase-A inhibitors and dopamine metabolism in rat caudatus: evidence that an increased cytosolic level of dopamine displaces reversible monoamine oxidase-A inhibitors in vivo.
The effects of reversible inhibitors of monoamine oxidase-A (moclobemide, Ro 41-1049, both 20 mg/kg, i.p., and brofaromine, 10 mg/kg, i.p.) on the outflow of dopamine (DA) and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) as well as of 5-hydroxyindoleacetic acid was investigated by trans-striatal microdialysis in rats. These drugs markedly increased the level of DA in the dialysis fluid by 100% of basal values and concomitantly reduced the output of 3,4-dihydroxy-phenylacetic acid and homovanillic acid by 90%. The presence of tetrodotoxin in the perfusion fluid decreased the basal DA outflow and virtually abolished the rise in DA efflux after moclobemide administration. On the other hand, tetrodotoxin did not counteract the DA outflow induced by Ro 4-1284 (1 mg/kg, i.p.), a tetrabenazine derivative which rapidly releases DA from vesicles and causes a massive increase in the concentration of extravesicular amine. The injection of Ro 4-1284 30 min after moclobemide, brofaromine or Ro 41-1049 induced a 6-fold increase in DA outflow, which was accompanied by a transient increase in 3,4-dihydroxyphenylacetic acid levels. This latter effect was more marked for moclobemide than for the other two reversible inhibitors tested and was not observed in rats given the irreversible inhibitor clorgyline (5 mg/kg, i.p.). These results support the view that a large increase in the concentration of endogenous substrates in the cytosol might displace reversible monoamine oxidase-A inhibitors from the enzyme active sites. Therefore, the microdialysis technique seems to be a reliable in vivo method for assessing the degree of reversibility of monoamine oxidase inhibitors.


Delineating the core regulatory elements crucial for directed cell migration by examining folic-acid-mediated responses.
Dictyostelium discoideum shows chemotaxis towards folic acid (FA) throughout vegetative growth, and towards cAMP during development. We determined the spatiotemporal localization of cytoskeletal and signaling molecules and investigated the FA-mediated responses in a number of signaling mutants to further our understanding of the core regulatory elements that are crucial for cell migration. Proteins enriched in the pseudopods during chemotaxis also relocalize transiently to the plasma membrane during uniform FA stimulation. In contrast, proteins that are absent from the pseudopods during migration redistribute transiently from the PM to the cytosol when cells are globally stimulated with FA. These chemotactic responses to FA were also examined in cells lacking the GTPases Ras C and G. Although Ras and phosphoinositide 3-kinase activity were significantly decreased in Ras G and Ras C/G nulls, these mutants still migrated towards FA, indicating that other pathways must support FA-mediated chemotaxis. We also examined the spatial movements of PTEN in response to uniform FA and cAMP stimulation in phospholipase C (PLC) null cells. The lack of PLC strongly influences the localization of PTEN in response to FA, but not cAMP. In addition, we compared the gradient-sensing behavior of polarized cells migrating towards cAMP to that of unpolarized cells migrating towards FA. The majority of polarized cells make U-turns when the cAMP gradient is switched from the front of the cell to the rear. Conversely, unpolarized cells immediately extend pseudopods towards the new FA source. We also observed that plasma membrane phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] levels oscillate in unpolarized cells treated with Latrunculin-A, whereas polarized cells had stable plasma membrane PtdIns(3,4,5)P3 responses toward the chemoattractant gradient source. Results were similar for cells that were starved for 4 hours, with a mixture of polarized and unpolarized cells responding to cAMP. Taken together, these findings suggest that similar components control gradient sensing during FA- and cAMP-mediated motility, but the response of polarized cells is more stable, which ultimately helps maintain their directionality.


Performance of mentally retarded forensic patients on the test of memory malingering.
The utility of the Test of Memory Malingering (TOMM) with mentally retarded forensic patients was assessed. Twenty-one adjudicated forensic inpatients, who had been diagnosed with mental retardation, were administered the TOMM. The majority of these patients also suffered from an Axis I mental disorder. The participants attained a mean score of 48.7 on Trial 2, with only 1 participant scoring below the standard cutoff for malingering (i.e., 45). The participants attained a mean score of 49.4 on the Retention Trial, with no participants falling below the cutoff for malingering. The results clearly indicate that mildly retarded forensic patients can perform well on the TOMM. The findings provide evidence that the TOMM can be used in the assessment of mildly retarded criminal defendants with little fear of obtaining false indications of malingering.


P. aeruginosa SGNH hydrolase-like proteins AlgJ and AlgX have similar topology but separate and distinct roles in alginate acetylation.
The O-acetylation of polysaccharides is a common modification used by pathogenic organisms to protect against external forces. Pseudomonas aeruginosa secretes the anionic, O-acetylated exopolysaccharide alginate during chronic infection in the lungs of cystic fibrosis patients to form the major constituent of a protective biofilm matrix. Four proteins have been implicated in the O-acetylation of alginate, AlgIJF and AlgX. To probe the biological function of AlgJ, we determined its structure to 1.83 Å resolution. AlgJ is a SGNH hydrolase-like protein, which while structurally similar to the N-terminal domain of AlgX exhibits a distinctly different electrostatic surface potential. Consistent with other SGNH hydrolases, we identified a conserved catalytic triad composed of D190, H192 and S288 and demonstrated that AlgJ exhibits acetylesterase activity in vitro. Residues in the AlgJ signature motifs were found to form an extensive network of interactions that are critical for O-acetylation of alginate in vivo. Using two different electrospray ionization mass spectrometry (ESI-MS) assays we compared the abilities of AlgJ and AlgX to bind and acetylate alginate. Binding studies using defined length polymannuronic acid revealed that AlgJ exhibits either weak or no detectable polymer binding while AlgX binds polymannuronic acid specifically in a length-dependent manner. Additionally, AlgX was capable of utilizing the surrogate acetyl-donor 4-nitrophenyl acetate to catalyze the O-acetylation of polymannuronic acid. Our results, combined with previously published in vivo data, suggest that the annotated O-acetyltransferases AlgJ and AlgX have separate and distinct roles in O-acetylation. Our refined model for alginate acetylation places AlgX as the terminal acetlytransferase and provides a rationale for the variability in the number of proteins required for polysaccharide O-acetylation.


Second cancers in survivors of hodgkin lymphoma: risks and recommendations.
Survivors of Hodgkin lymphoma (HL) who received certain oncology treatment years ago may have a lifelong risk for second cancers. This article reviews evidence-based data about subsequent solid tumor development in HL survivors. Regarding the development of solid cancer, a significant difference existed between one study group of HL survivors and same-aged people from the general population. HL treatments using combinations of radiation and chemotherapy and those using extended-field radiation have been suggested to pose an increased risk for second cancers. Changes in treatment for HL reflect researchers' attempts to reduce late complications of oncology treatment. Oncology nurses are in a unique position to counsel patients with HL and survivors regarding the importance of follow-up assessments, cancer-prevention practices, and screening recommendations. Ultimately, results will ensure that HL survivors have a better chance of wellness.


Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 Study.
Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages.


Crystallization characteristics and chemical bonding properties of nickel carbide thin film nanocomposites.
The crystal structure and chemical bonding of magnetron-sputtering deposited nickel carbide Ni₁-xCx (0.05 ⩽ x⩽0.62) thin films have been investigated by high-resolution x-ray diffraction, transmission electron microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, and soft x-ray absorption spectroscopy. By using x-ray as well as electron diffraction, we found carbon-containing hcp-Ni (hcp-NiCy phase), instead of the expected rhombohedral-Ni₃C. At low carbon content (4.9 at%), the thin film consists of hcp-NiCy nanocrystallites mixed with a smaller amount of fcc-NiCx. The average grain size is about 10-20 nm. With the increase of carbon content to 16.3 at%, the film contains single-phase hcp-NiCy nanocrystallites with expanded lattice parameters. With a further increase of carbon content to 38 at%, and 62 at%, the films transform to x-ray amorphous materials with hcp-NiCy and fcc-NiCx nanodomain structures in an amorphous carbon-rich matrix. Raman spectra of carbon indicate dominant sp(2) hybridization, consistent with photoelectron spectra that show a decreasing amount of C-Ni phase with increasing carbon content. The Ni 3d-C 2p hybridization in the hexagonal structure gives rise to the salient double-peak structure in Ni 2p soft x-ray absorption spectra at 16.3 at% that changes with carbon content. We also show that the resistivity is not only governed by the amount of carbon, but increases by more than a factor of two when the samples transform from crystalline to amorphous.


The Eastern Association for the Surgery of Trauma's Injury Control and Violence Prevention Committee's annual distracted driving outreach event: Evaluating attitude and behavior change in high school students.
The National Center for Statistics and Analysis reports at least eight deaths and 1,160 daily injuries due to distracted driving (DD) in the United States. Drivers younger than 20 years are most likely to incur a distraction-related fatal crash. We aimed to determine short- and long-term impact of a multimodal educational program including student-developed interventions, simulated driving experiences, and presentations by law enforcement and medical personnel. A single-day program aimed at teen DD prevention was conducted at a high school targeting students aged 15 years to 19 years old. Students were surveyed before, after, and at 6 weeks. We surveyed age, gender, knowledge, and experience regarding DD. Summary statistics were obtained at each survey time point. Bivariate and multivariable analysis were conducted to assess whether change in responses varied over time points. Multivariable models were adjusted for sex and urban and rural driving. Preintervention, postintervention, and 6-week follow-up surveys were completed by 359, 272 (76%), and 331 (92%) students, respectively. At baseline and 6-week follow-up, the most frequent passenger-reported DD behaviors were cell phone (63% [63% at follow-up) and radio use (61% [63%]). Similarly, the most frequent driver-reported DD behaviors were cell phone (68% [72%]) and radio use (79% [80%]). When students were asked, "How likely are you to use your cell phone while driving?" they answered "never" 35%, 70%, and 46% on the preintervention, postintervention, and 6-week surveys. They were less likely to report consequences to be worse or change in attitude to a great extent at 6 weeks (p < 0.01). Gender and urban or rural driving were not significantly associated with responses. While DD education may facilitate short-term knowledge and attitude changes, there appears to be no lasting effect. Research should be focused toward strategies for longer-term impact. Therapeutic study, level II.


Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma.
The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A + AVD from a US healthcare payer perspective. The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1. The ICER for A + AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure. The ICER for A + AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A + AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.


Mechanisms and inhibitors of nicotinamide N-methyltransferase.
Nicotinamide N-methyltransferase (NNMT) plays an important role in diverse biological processes by regulating methylation potential and the degradation of nicotinamide. Meanwhile, the aberrant expression of NNMT has been implicated in multiple cancers, metabolic and liver diseases. Therefore, there has been an emerging interest in assessing NNMT as a potential therapeutic target and discovering NNMT inhibitors over the past 5 years. Herein, we focus on the recognition, mechanism, and inhibitors of NNMT with emphasis on key advancements in the field. We also discuss future directions for the development of NNMT inhibitors.


A focus of dogs and Rickettsia massiliae-infected Rhipicephalus sanguineus in California.
A recurrent focus of Rhipicephalus sanguineus infestation was investigated in a suburban area of southern California after reports of suspected Rocky Mountain spotted fever in two dogs on the same property. Abundant quantities of Rh. sanguineus were collected on the property and repeatedly from each dog, and Rickettsia massiliae DNA was detected by polymerase chain reaction (PCR). Whole blood and serum samples from four dogs were tested by using PCR and microimmunofluorescent assay for antibodies against spotted fever group rickettsiae. Serum samples from all four dogs contained antibodies reactive with R. massiliae, R. rhipicephali, R. rickettsii, and 364D Rickettsia but no rickettsial DNA was detected by PCR of blood samples. Serum cross-absorption and Western blot assays implicated R. massiliae as the most likely spotted fever group rickettsiae responsible for seropositivity. To our knowledge, this is the first detection of R. massiliae in ticks in California.


Heat-related emergency hospitalizations for respiratory diseases in the Medicare population.
The heat-related risk of hospitalization for respiratory diseases among the elderly has not been quantified in the United States on a national scale. With climate change predictions of more frequent and more intense heat waves, it is of paramount importance to quantify the health risks related to heat, especially for the most vulnerable. To estimate the risk of hospitalization for respiratory diseases associated with outdoor heat in the U.S. elderly. An observational study of approximately 12.5 million Medicare beneficiaries in 213 United States counties, January 1, 1999 to December 31, 2008. We estimate a national average relative risk of hospitalization for each 10°F (5.6°C) increase in daily outdoor temperature using Bayesian hierarchical models. We obtained daily county-level rates of Medicare emergency respiratory hospitalizations (International Classification of Diseases, Ninth Revision, 464-466, 480-487, 490-492) in 213 U.S. counties from 1999 through 2008. Overall, each 10°F increase in daily temperature was associated with a 4.3% increase in same-day emergency hospitalizations for respiratory diseases (95% posterior interval, 3.8, 4.8%). Counties' relative risks were significantly higher in counties with cooler average summer temperatures. We found strong evidence of an association between outdoor heat and respiratory hospitalizations in the largest population of elderly studied to date. Given projections of increasing temperatures from climate change and the increasing global prevalence of chronic pulmonary disease, the relationship between heat and respiratory morbidity is a growing concern.


What do we know about the application of the Mental Capacity Act (2005) in healthcare practice regarding decision-making for frail and older people? A systematic literature review.
In England and Wales, decision-making in cases of uncertain mental capacity is regulated by the Mental Capacity Act 2005. The Act provides a legal framework for decision-making for adults (16 and over) who are shown to lack capacity and where best interest decisions need to be made on their behalf. Frail older people with cognitive impairments represent a growing demographic sector across England and Wales for whom the protective principles of the Act have great relevance, as they become increasingly dependent on the care of others. However, while the Act articulates core principles, applying the Act in everyday healthcare contexts raises challenges for care providers in terms of interpretation and application. This paper presents a review of the published evidence documenting the use of the Act in healthcare practice, with particular reference to frail older people. Our aim was to identify, review and critically evaluate published empirical studies concerned with the implementation and application of the Act in healthcare settings. A systematic approach was undertaken with pre-determined exclusion and inclusion criteria applied across five electronic bibliographic databases combined with a manual search of specific journals. This review reports on 38 empirical sources which met the inclusion criteria published between 2005 and 2013. From the 38 sources, three descriptive themes were identified: knowledge and understanding, implementation and tensions in applying the Act, and alternative perspectives of the Act. There is a need for improved knowledge and conceptualisation to enable successful incorporation of the Act into everyday care provision. Inconsistencies in the application of the Act are apparent across a variety of care settings. This review suggest staff need more opportunities to engage, learn and implement the Act, in order for it to have greater resonance to their individual practice and ultimately benefit patient care.


Initial psychometric properties of the experiences questionnaire: validation of a self-report measure of decentering.
Decentering is defined as the ability to observe one's thoughts and feelings as temporary, objective events in the mind, as opposed to reflections of the self that are necessarily true. The Experiences Questionnaire (EQ) was designed to measure both decentering and rumination but has not been empirically validated. The current study investigated the factor structure of the EQ in both undergraduate and clinical populations. A single, unifactorial decentering construct emerged using 2 undergraduate samples. The convergent and discriminant validity of this decentering factor was demonstrated in negative relationships with measures of depression symptoms, depressive rumination, experiential avoidance, and emotion regulation. Finally, the factor structure of the EQ was replicated in a clinical sample of individuals in remission from depression, and the decentering factor evidenced a negative relationship to concurrent levels of depression symptoms. Findings from this series of studies offer initial support for the EQ as a measure of decentering.


Minimal acute rejection in pediatric lung transplantation--does it matter?
In adult lung transplantation, a single minimal AR episode is a significant predictor of BOS independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine whether isolated single AR episodes are associated with an increased BOS risk in children. Risk factors for BOS, death, or re-transplantation, and a combined outcome of BOS, death, or re-transplantation were assessed. Original data included 577 patients (<21 yr of age). A total of 383 subjects were eligible for the study. Fifteen percent of patients developed BOS, and 13% of patients either died or underwent re-transplant within one-yr post-transplant. In the multivariable survival model for time to BOS, there was no significant risk to developing BOS after a single minimal AR (A1) episode (HR 1.7, 95% CI 0.64-4.8; p=0.28). Even after a second minimal AR episode, no significant risk for BOS was appreciated. However, a single episode of mild AR (A2) was associated with twice the risk of BOS within one-yr post-transplant. In this select cohort, a single minimal AR episode was not associated with an increased risk for BOS within one yr following lung transplantation, in contrast to previous reports in adults.


Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer.
We incorporated cetuximab, a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR), into the induction therapy and subsequent chemoradiotherapy of head and neck cancer (HNC). Patients with locally advanced HNC, including squamous and undifferentiated histologies, were treated with docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and cetuximab 250 mg/m2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m2 and cetuximab weekly (XPE), and maintenance cetuximab for 6 months. Quality of life (QOL) was assessed using Functional Assessment of Cancer Therapy-Head and Neck. In situ hybridization (ISH) for human papillomavirus (HPV), immunohistochemistry for p16, and fluorescence ISH for EGFR gene copy number were performed on tissue microarrays. Of 39 enrolled patients, 36 had stage IV disease and 23 an oropharyngeal primary. Acute toxicities during TPE included neutropenic fever (10%) and during XPE, grade 3 or 4 oral mucositis (54%) and hypomagnesemia (39%). With a median follow-up of 36 months, 3-year progression-free survival and overall survival were 70% and 74%, respectively. Eight patients progressed in locoregional sites, three in distant, and one in both. HPV positivity was not associated with treatment efficacy. No progression-free patient remained G-tube dependent. The H&N subscale QOL scores showed a significant decrement at 3 months after XPE, which normalized at 1 year. This cetuximab-containing regimen resulted in excellent long-term survival and safety, and warrants further evaluation in both HPV-positive and -negative HNC.


Differential responses of soil bacteria, fungi, archaea and protists to plant species richness and plant functional group identity.
Plants are known to influence belowground microbial community structure along their roots, but the impacts of plant species richness and plant functional group (FG) identity on microbial communities in the bulk soil are still not well understood. Here, we used 454-pyrosequencing to analyse the soil microbial community composition in a long-term biodiversity experiment at Jena, Germany. We examined responses of bacteria, fungi, archaea, and protists to plant species richness (communities varying from 1 to 60 sown species) and plant FG identity (grasses, legumes, small herbs, tall herbs) in bulk soil. We hypothesized that plant species richness and FG identity would alter microbial community composition and have a positive impact on microbial species richness. Plant species richness had a marginal positive effect on the richness of fungi, but we observed no such effect on bacteria, archaea and protists. Plant species richness also did not have a large impact on microbial community composition. Rather, abiotic soil properties partially explained the community composition of bacteria, fungi, arbuscular mycorrhizal fungi (AMF), archaea and protists. Plant FG richness did not impact microbial community composition; however, plant FG identity was more effective. Bacterial richness was highest in legume plots and lowest in small herb plots, and AMF and archaeal community composition in legume plant communities was distinct from that in communities composed of other plant FGs. We conclude that soil microbial community composition in bulk soil is influenced more by changes in plant FG composition and abiotic soil properties, than by changes in plant species richness per se.


Recurrent processing enhances visual awareness but is not necessary for fast categorization of natural scenes.
Humans are rapid in categorizing natural scenes. Electrophysiological recordings reveal that scenes containing animals can be categorized within 150 msec, which has been interpreted to indicate that feedforward flow of information from V1 to higher visual areas is sufficient for visual categorization. However, recent studies suggest that recurrent interactions between higher and lower levels in the visual hierarchy may also be involved in categorization. To clarify the role of recurrent processing in scene categorization, we recorded EEG and manipulated recurrent processing with object substitution masking while the participants performed a go/no-go animal/nonanimal categorization task. The quality of visual awareness was measured with a perceptual awareness scale after each trial. Masking reduced the clarity of perceptual awareness, slowed down categorization speed for scenes that were not clearly perceived, and reduced the electrophysiological difference elicited by animal and nonanimal scenes after 150 msec. The results imply that recurrent processes enhance the resolution of conscious representations and thus support categorization of stimuli that are difficult to categorize on the basis of the coarse feedforward representations alone.


Tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.
Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilizes the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clinical results observed in the last years, the long-term effects of imatinib and its ability to completely eradicate CML are still unknown. Moreover, similar to many other anti-cancer drugs, clinical resistance to imatinib has emerged. In this review we will discuss the in vitro and in vivo results obtained with the novel tyrosine kinase inhibitors developed to overcome imatinib resistance in Bcr-Abl expressing hematologiocal disorders.


[Effect of the medium composition and cultivation conditions on sporulation in chemolithotrophic bacteria].
The possibility of controlling endospore formation by changing cultivation conditions was for the first time shown in acidophilic chemolithotrophic bacteria Sulfobacillus thermosulfidooxidans type strain 1269 and the thermotolerant strain K1 formerly described as "S. thermosulfidooxidans subsp. thermotolerans". Suppression of sporulation occurred when these strains were cultured in Manning's liquid medium with yeast extract. This medium was optimized by gradually reducing the concentrations of ferrous iron salts (the source of energy), phosphorous, nitrogen, and yeast extract and simultaneously increasing the concentrations of calcium, magnesium, and manganese (the elements important for sporogenesis) to attain higher yields of endospores by strains 1269 and K1. As a result, a new medium A was proposed, in which the life cycle of the strains studied culminated in sporulation at a level of 45 and 60%, respectively, of the total cell number. In a series of additional tests, the growth temperature and medium pH were adjusted to obtain the maximum yield of endospores. The optimal ranges found were 40-50 degrees C and pH 1.8-2.2 for strain 1269 and 35-40 degrees C and pH 2.5-2.7 for strain K1. An even higher yield of endospores, amounting to 55 and 75% for strains 1269 and K1, respectively, was obtained when the above growth conditions were combined (growth on medium A at optimal temperatures and pH). Our results suggest a new approach to optimizing sporulation by acidophilic chemolithotrophs, which consists in limiting the energy and nutrient sources and using temperature and pH values within the tolerance bounds of these cultures but outside their growth of optimum ranges.


Antimicrobial resistance in Shigella species isolated in Dakar, Senegal (2004-2006).
From May 2004 to October 2006, a prospective study was carried out in Dakar, Senegal, to update information about the antimicrobial susceptibility of Shigella spp. isolated from stool specimens. Among the 165 non-duplicate strains collected, 81 (49%) were identified as Shigella flexneri, 75 (45%) as Shigella sonnei, 5 (3%) as Shigella boydii, and 4 (2%) as Shigella dysenteriae. Disk diffusion testing revealed that the majority of isolates were resistant to sulphonamides, trimethoprim-sulfamethoxazole, streptomycin, and tetracycline (respective overall resistance rates: 90, 90, 96, and 94%). More than half of the S. flexneri isolates were resistant to amoxicillin, amoxicillin-clavulanic acid, and chloramphenicol (respective resistance rates: 59, 58, and 52%), and almost all of the S. sonnei isolates were susceptible to these antimicrobials (respective resistance rates: 4, 1, and 4%). Only one isolate (belonging to the species S. sonnei) was resistant to nalidixic acid and displayed reduced susceptibility to ciprofloxacin.


An investigation of professionalism reflected by student comments on formative virtual patient encounters.
This study explored the use of virtual patient generated data by investigating the association between students' unprofessional patient summary statements, which they entered during an on-line virtual patient case, and detection of their future unprofessional behavior. At the USUHS, students complete a number of virtual patient encounters, including a patient summary, to meet the clerkship requirements of Internal Medicine, Family Medicine, and Pediatrics. We reviewed the summary statements of 343 students who graduated in 2012 and 2013. Each statement was rated with regard to four features: Unprofessional, Professional, Equivocal (could be construed as unprofessional), and Unanswered (students did not enter a statement). We also combined Unprofessional and Equivocal into a new category to indicate a statement receiving either rating. We then examined the associations of students' scores on these categories (i.e. whether received a particular rating or not) and Expertise score and Professionalism score reflected by a post-graduate year one (PGY-1) program director (PD) evaluation form. The PD forms contained 58 Likert-scale items designed to measure the two constructs (Expertise and Professionalism). The inter-rater reliability of statements coding was high (Cohen's Kappa = .97). The measure of receiving an Unprofessional or Equivocal rating was significantly correlated with lower Expertise score (r = -.19, P < .05) as well as lower Professionalism score (r = -.17, P < .05) during PGY-1. Incident reports and review of routine student evaluations are what most schools rely on to identify the majority of professionalism lapses. Unprofessionalism reflected in student entries may provide additional markers foreshadowing subsequent unprofessional behavior.


Prevalence of complementary and alternative medicine use in cancer patients during treatment.
To assess complementary and alternative medicine (CAM) therapies being utilized by cancer patients during treatment and communication about CAM usage between the patient and physician. Newly diagnosed cancer patients receiving chemotherapy or radiation therapy were recruited to complete a CAM survey within 2 weeks after the termination of treatment. Patients were queried on which CAM modalities they utilized and whether or not they were discussed with either their oncologist or primary care physician. Of the patients surveyed, 91% reported using at least one form of CAM. The most widely used forms of CAM were prayer, relaxation and exercise. CAM users tended to be women chemotherapy patients with at least a high school education. Of the patients using CAM, 57% discussed the use of at least one of these therapies with their oncologist or primary care physician. The most frequent CAM modalities discussed with at least one physician were diets, massage, and herbal medicine. An overwhelming proportion of cancer patients are using CAM, particularly prayer, relaxation, and exercise. However, patients may not discuss the use of CAMs at all or fully with their physician; if they do, it is most likely to be their oncologist, but not about the most frequently used CAMs. Future research needs to assess effective ways for oncologists to gather information about CAM usage by patients during allopathic treatment and discern ways these therapies may enhance or interfere with traditional cancer treatments.


How cortical waves drive fission of motile cells.
Cytokinesis-the division of a cell into two daughter cells-is a key step in cell growth and proliferation. It typically occurs in synchrony with the cell cycle to ensure that a complete copy of the genetic information is passed on to the next generation of daughter cells. In animal cells, cytokinesis commonly relies on an actomyosin contractile ring that drives equatorial furrowing and separation into the two daughter cells. However, also contractile ring-independent forms of cell division are known that depend on substrate-mediated traction forces. Here, we report evidence of an as yet unknown type of contractile ring-independent cytokinesis that we termed wave-mediated cytofission. It is driven by self-organized cortical actin waves that travel across the ventral membrane of oversized, multinucleated Dictyostelium discoideum cells. Upon collision with the cell border, waves may initiate the formation of protrusions that elongate and eventually pinch off to form separate daughter cells. They are composed of a stable elongated wave segment that is enclosed by a cell membrane and moves in a highly persistent fashion. We rationalize our observations based on a noisy excitable reaction-diffusion model in combination with a dynamic phase field to account for the cell shape and demonstrate that daughter cells emerging from wave-mediated cytofission exhibit a well-controlled size.


Biliary tract obstruction in chronic pancreatitis.
Bile duct strictures are a common complication in patients with advanced chronic pancreatitis and have a variable clinical presentation ranging from an incidental finding to overt jaundice and cholangitis. The diagnosis is mostly made during investigations for abdominal pain but jaundice may be the initial clinical presentation. The jaundice is typically transient but may be recurrent with a small risk of secondary biliary cirrhosis in longstanding cases. The management of a bile duct stricture is conservative in patients in whom it is an incidental finding as the risk of secondary biliary cirrhosis is negligible. Initial conservative treatment is advised in patients who present with jaundice as most will resolve once the acute on chronic attack has subsided. A surgical biliary drainage is indicated when there is persistent jaundice for more than one month or if complicated by secondary gallstones or cholangitis. The biliary drainage procedure of choice is a choledocho-jejunostomy which may be combined with a pancreaticojejunostomy in patients who have associated pain. Since many patients with chronic pancreatitis have an inflammatory mass in the head of the pancreas, a Frey procedure is indicated but a resection should be performed when there is concern about a malignancy. Temporary endoscopic stenting is reserved for cholangitis while an expandable metal stent may be indicated in patients with severe co-morbid disease.


Organellar channels and transporters.
Decades of intensive research have led to the discovery of most plasma membrane ion channels and transporters and the characterization of their physiological functions. In contrast, although over 80% of transport processes occur inside the cells, the ion flux mechanisms across intracellular membranes (the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, mitochondria, chloroplasts, and vacuoles) are difficult to investigate and remain poorly understood. Recent technical advances in super-resolution microscopy, organellar electrophysiology, organelle-targeted fluorescence imaging, and organelle proteomics have pushed a large step forward in the research of intracellular ion transport. Many new organellar channels are molecularly identified and electrophysiologically characterized. Additionally, molecular identification of many of these ion channels/transporters has made it possible to study their physiological functions by genetic and pharmacological means. For example, organellar channels have been shown to regulate important cellular processes such as programmed cell death and photosynthesis, and are involved in many different pathologies. This special issue (SI) on organellar channels and transporters aims to provide a forum to discuss the recent advances and to define the standard and open questions in this exciting and rapidly developing field. Along this line, a new Gordon Research Conference dedicated to the multidisciplinary study of intracellular membrane transport proteins will be launched this coming summer.


Renal angiotensin receptor mapping in obese spontaneously hypertensive rats.
Obese spontaneously hypertensive rats (SHR) develop nephropathy with severe proteinuria, but lean littermates do not develop renal disease. Intrarenal angiotensin has been suggested to contribute to nephropathy in other experimental models. We examined the regulation of angiotensin receptors as a reflection of target tissue response to possible changes in the renin-angiotensin system. We visualized angiotensin receptors in kidneys of 6-8-month-old obese SHR and their lean littermates. Both obese and lean rats were hypertensive as determined by tail-cuff or by direct measurement. Histologic studies showed early glomerular sclerosis in obese but not lean rats. Autoradiographic visualization of angiotensin receptor binding sites in both obese and lean SHR showed glomeruli and medullary rays having the highest levels of binding with additional diffuse labeling in cortex and outer medulla. In obese rats, binding was reduced relative to lean littermates, particularly in the medulla, while intense binding in glomeruli was preserved. Loss of receptors did not reflect tissue damage, since the medulla showed no pathological changes. Biochemical assays of the binding of subtype-selective antagonists to 125I-angiotensin sites in intact sections showed that both losartan-sensitive and PD 123319-sensitive sites were decreased in nephrotic obese rats. We conclude that specific binding sites for angiotensin are decreased in obese SHR with early glomerular sclerosis, suggesting that angiotensin receptors may be regulated by pathogenic processes in this model of renal disease.


Parallel decreases in the expression of receptors for insulin and insulin-like growth factor I in a mutant human fibroblast line.
The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. The similar subunit structures of these two types of receptors suggested that their genetic expression might be affected by common genetic defects. We have examined this possibility in an insulin-resistant, diabetic patient who exhibits decreased insulin binding activity. The receptors for IGF-I and insulin in skin fibroblasts from this patient were affinity labeled with 125I-IGF-I and 125I-insulin, respectively, and visualized by electrophoresis and autoradiography in polyacrylamide gels. Control fibroblasts exhibited the usual affinity labeling of the disulfide-linked Mr = 350,000 insulin and IGF-I receptor structures. The intensity of labeling of both receptor types in the patient's fibroblasts was less than in control fibroblasts. Binding data indicated that this decrease is due to a decreased receptor number with little or no decrease in affinity for the respective ligands. The high-affinity IGF-II receptor in fibroblasts affinity labeled with 125I-IGF-II or 125I-IGF-I consists of a single polypeptide not disulfide linked to any other membrane component. The molecular size and intensity of labeling of the IGF-II receptor in the patient's fibroblasts were unaltered when compared with those of controls. These observations suggest that a common genetic defect alters the expression of the homologous receptor structures for insulin and IGF-I.


A model (in)validation approach to gait classification.
This paper addresses the problem of human gait classification from a robust model (in)validation perspective. The main idea is to associate to each class of gaits a nominal model, subject to bounded uncertainty and measurement noise. In this context, the problem of recognizing an activity from a sequence of frames can be formulated as the problem of determining whether this sequence could have been generated by a given (model, uncertainty, and noise) triple. By exploiting interpolation theory, this problem can be recast into a nonconvex optimization. In order to efficiently solve it, we propose two convex relaxations, one deterministic and one stochastic. As we illustrate experimentally, these relaxations achieve over 83 percent and 86 percent success rates, respectively, even in the face of noisy data.


Experimental demonstration of coupled-resonator-induced-transparency in silicon-on-insulator based ring-bus-ring geometry.
We experimentally demonstrate coupled-resonator-induced-transparency (CRIT) phenomenon in ring-bus-ring (RBR) geometry synergistically integrated with Mach-Zehnder interferometer (MZI). The RBR consists of two detuned resonators indirectly coupled through a center bus waveguide. The transparency is obtained by increasing the light intercavity interaction through tailoring the RBR phase response while ensuring balanced MZI operation. In this work, a CRIT resonance with a quality factor of ~18,000 is demonstrated with cavity size detuning of ~0.035% and power coupling of ~60%, which are in good agreement with the theory.


An improved method for the rescue of recombinant Newcastle disease virus.
Reverse genetics has been used to generate recombinant Newcastle disease virus with enhanced immunogenic properties for vaccine development. The system, which involves co-transfecting the viral antigenomic plasmid with three helper plasmids into a T7 RNA polymerase-expressing cell to produce viral progenies, poses a great challenge. We have modified the standard transfection method to improve the transfection efficiency of the plasmids, resulting in a higher titer of virus progeny production. Two transfection reagents (i.e., lipofectamine and polyethylenimine) were used to compare the transfection efficiency of the four plasmids. The virus progenies produced were quantitated with flow cytometry analysis of the infectious virus unit. The modified transfection method increased the titer of virus progenies compared with that of the standard transfection method.


Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage.
Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC-HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of glycerol-induced IVH and analyzed autopsy samples from premature infants. We found that total HA levels were comparable in both preterm rabbit pups and human infants with and without IVH, but HA receptors--CD44, TLR2, TLR4--were elevated in the forebrain of both humans and rabbits with IVH. Hyaluronidase treatment of rabbits with IVH reduced CD44 and TLR4 expression, proinflammatory cytokine levels, and microglia infiltration. It also promoted OPC maturation, myelination, and neurological recovery. HC-HA and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC-HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH. Significance statement: Approximately 12,000 premature infants develop IVH every year in the United States, and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The onset of IVH induces inflammation of the periventricular white matter, which results in arrested maturation of OPCs and myelination failure. HA is a major component of the extracellular matrix of the brain, which regulates inflammation through CD44 and TLR2/4 receptors. Here, we show two mechanism-based strategies that effectively enhanced myelination and neurological recovery in preterm rabbit model of IVH. First, degrading HA by hyaluronidase treatment reduced CD44 and TLR4 expression, proinflammatory cytokines, and microglial infiltration, as well as promoted oligodendrocyte maturation and myelination. Second, intraventricular injection of HA oligosaccharide reduced inflammation and enhanced myelination, conceivably by depleting HC-HA levels.


A tale of two methods: comparing regression and instrumental variables estimates of the effects of preschool child care type on the subsequent externalizing behavior of children in low-income families.
We apply instrumental variables (IV) techniques to a pooled data set of employment-focused experiments to examine the relation between type of preschool childcare and subsequent externalizing problem behavior for a large sample of low-income children. To assess the potential usefulness of this approach for addressing biases that can confound causal inferences in child care research, we compare instrumental variables results with those obtained using ordinary least squares (OLS) regression. We find that our OLS estimates concur with prior studies showing small positive associations between center-based care and later externalizing behavior. By contrast, our IV estimates indicate that preschool-aged children with center care experience are rated by mothers and teachers as having fewer externalizing problems on entering elementary school than their peers who were not in child care as preschoolers. Findings are discussed in relation to the literature on associations between different types of community-based child care and children's social behavior, particularly within low-income populations. Moreover, we use this study to highlight the relative strengths and weaknesses of each analytic method for addressing causal questions in developmental research.


The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data.
To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 and 2010. The age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584 000 were blind in 2000, in comparison with 170 000 who were blind in 2010. Despite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.


Decompression of Lumbar Central Spinal Canal Stenosis Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.
This was a retrospective clinical series. The objective of this study was to evaluate radiologic changes in central spinal canal dimensions following minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) with placement of a static or an expandable interbody device. MIS-TLIF is used to treat lumbar degenerative diseases and low-grade spondylolisthesis. MIS-TLIF enables direct and indirect decompression of lumbar spinal stenosis, with patients experiencing relief from radiculopathy and neurogenic claudication. However, the effects of MIS-TLIF on the central spinal canal are not well-characterized. We identified patients who underwent MIS-TLIF for degenerative lumbar spondylolisthesis and concurrent moderate to severe spinal stenosis. We selected patients who had both preoperative and postoperative magnetic resonance imaging (MRI) and upright lateral radiographs of the lumbar spine. Measurements on axial T2-weighted MRI scans include anteroposterior and transverse dimensions of the dural sac and osseous spinal canal. Measurements on radiographs include disk height, neural foraminal height, segmental lordosis, and spondylolisthesis. We made pairwise comparisons between each of the central canal dimensions and lumbar sagittal segmental radiologic outcome measures relative to their corresponding preoperative values. Correlation coefficients were used to quantify the association between changes in lumbar sagittal segmental parameters relative to changes in radiologic outcomes of central canal dimensions. Statistical analysis was performed for "all patients" and further stratified by interbody device subgroups (static and expandable). Fifty-one patients (age 60.4 y, 68.6% female) who underwent MIS-TLIF at 55 levels (65.5% at L4-L5) were included in the analysis. Expandable interbody devices were used in 45/55 (81.8%) levels. Mean duration from surgery to postoperative MRI scan was 16.5 months (SD 11.9). MIS-TLIF was associated with significant improvements in dural sac dimensions (anteroposterior +0.31 cm, transverse +0.38 cm) and osseous spinal canal dimensions (anteroposterior +0.16 cm, transverse +0.32 cm). Sagittal lumbar segmental parameters of disk height (+0.56 cm), neural foraminal height (+0.35 cm), segmental lordosis (+4.26 degrees), and spondylolisthesis (-7.5%) were also improved following MIS-TLIF. We did not find meaningful associations between the changes in central canal dimensions relative to the corresponding changes in any of the sagittal lumbar segmental parameters. Stratified analysis by interbody device type (static and expandable) revealed similar within-group changes as in the overall cohort and minimal between-group differences. MIS-TLIF is associated with radiologic decompression of neural foraminal and central spinal canal stenosis. The mechanism for neural foraminal and central canal decompression is likely driven by a combination of direct and indirect corrective techniques.


Varicose veins: new trends in treatment in a Vascular Surgery Unit.
Less invasive techniques such as foam sclerotherapy, endovenous laser or radiofrequency ablation have recently been introduced as a valid alternative to surgery for the treatment of varicose veins (VVs). We retrospectively reviewed our experience in the treatment of VVs with particular attention to how our therapeutic approach has changed over the last years. Data of all patients consecutively treated from September 1st 2013 to July 31st 2015 for both primitive and recurrent VVs were retrospectively collected and analyzed. Statistical analysis was performed using the software JMP 5.1.2 (SAS Institute). A total of 409 legs in 378 patients were treated. The percentage of stripping of the great saphenous veins (GSV) for primary VVs has decreased over the years (67% in 2013 vs 15.2% in 2015), differently from what happened to the percentage of RFA of the GSV (14.3% vs. 31.5% respectively in 2013 and in 2015) and to the percentage of legs treated with the A.S.V.A.L. technique (8.7% vs. 31.5% respectively in 2013 and in 2015). Likewise, in 2013 most procedures were performed using spinal anesthesia (77.5%), while in 2015 the most used anesthetic techniques were both the local anesthesia and the local anesthesia with conscious sedation (35.9% and 29.3% respectively). Postoperative course was uneventful in all cases but seven (1.7%). At follow-up (median 16.9 months, IQR 7.5-22.6 months), neither major adverse events nor deaths were recorded. During the years of our experience, we observed a trend towards a less invasive approach for the treatment of VVs, with safe and effective results. Ablation Radiofrequency, Stripping, Varicose veins.


A shockwave approach for web-based clinical motion analysis.
Advances in Internet connectivity and personal multimedia computing have created opportunities for integrating simple motion analysis into clinical practice. The Macromedia Shockwave environment provides tools for creating media-rich software that runs within a Web browser. For this project, clinical motion analysis software was created using Shockwave that can load digital video clips of a client's motion, step/shuttle/play through the clip, superimpose a grid over the video image, measure relative joint angles, scale to a linear factor, measure distances, and measure average velocities. After installing the Shockwave and Quicktime video plug-ins, the Motion Analysis Tools-Shockwave program runs directly from a Web page hyperlink. Program testing involved comparing angle measurements, linear distances, stride length, and walking speed among six video clips. The first three clips were of a transtibial prosthesis being carried through the field of view (640 x 480, 320 x 240, 320 x 240 enlarged to 640 x 480). The second set of three clips was of a metal square carried through the field of view. Average root mean square errors were 2.0 degrees for angle measures and 1.2 cm for length measures. Stride length standard deviation was 4.6 cm (mean length = 212.1 cm). Average walking speed standard deviation was 0.015 m/s (mean speed = 1.15 m/s). The test results were consistent with video motion analysis results and within an acceptable range for clinical design-making. This Web-based motion analysis approach provides a useful tool for ubiquitous, quantitative, clinical gait analysis.


Solitary cerebellar metastases: analysis of 11 cases.
Solitary cerebellar metastatic tumors are rarely reported in the literature. We reviewed 240 posterior fossa tumors treated in the past eight years. There were 11 cases of solitary metastases in the cerebellum. The primary tumor was lung cancer in five cases and breast carcinoma in two cases; the remaining three cases had colon cancer, nasopharyngeal carcinoma (NPC) and Ewing's sarcoma, respectively. All patients underwent craniectomy and gross total excision of the tumor. Seven patients survived less than one year, two cases died in the second year, and one case of NPC survived for more than two years. The only survival is a case of Ewing's sarcoma who underwent surgery 14 months ago. The symptoms and signs of all patients improved satisfactorily after surgery. Four patients received postoperative irradiation to the posterior fossa and two cases of lung cancer had a thoracotomy for the primary lung lesion; however, the survival period was not prolonged. We suggest that a cancer patient or a patient in the fifth to seventh decades of life presenting headache, gait disturbance and vomiting should promptly undergo a computed tomography (CT) scan of the head. In selected cases, surgical intervention for solitary metastatic tumors in the tiny posterior fossa may be the best initial treatment. Adjuvant therapies should then be added according to the type of tumor.


The initial vascular access type contributes to inflammation in incident hemodialysis patients.
Background. The contribution of the hemodialysis (HD) vascular access type to inflammation is unclear. Methods. We conducted a prospective observational study in an incident HD population. C-reactive protein (CRP), interleukin-6 (IL-6), and interferon-γ-induced protein (IP-10) were measured before and at 6-time points after access placement for 1 year. Results. Sixty-four incident HD patients were included (tunneled catheter (TC), n = 40, arteriovenous fistula (AVF), n = 14, and arteriovenous graft (AVG), n = 10). A mixed effects model was performed to adjust for age, sex, race, coronary artery disease, diabetes mellitus, infections, access thrombosis, initiation of HD, and days after access surgery. In comparison to AVFs, the presence of a TC was associated with significantly higher levels of CRP (P = 0.03), IL-6 (P = 0.07), and IP-10 (P = 0.03). The presence of an AVG was associated with increases in CRP (P = 0.01) and IP-10 (P = 0.07). Conclusions. Patients who initiate HD with a TC or an AVG have a heightened state of inflammation, which may contribute to the excess 90-day mortality after HD initiation.